The goal of this Phase I research is to design, synthesize, develop, and evaluate the in vitro efficacy of a new class of polymeric "targeted" prodrugs of AZT. The overall objective of this program is to create new anti-AIDS prodrugs which will possess markedly enhanced antiviral activity, low toxicity, target-accessibility, and sustained drug release. The Phase I plan is based on the promising in vitro antiviral activity obtained by us with AZT-polymer, conjugate I, and is modeled after our prior work on the development of Pt(trans-DACH)carboxysaccharide antitumor complexes which exhibited substantially improved antitumor properties when compared to their monomeric analogs. In Phase I research anti-retroviral properties of AZT conjugate I will be optimized; e.g. by increasing the AZT content in the conjugate. Activity of the conjugate will be evaluated in vitro using HIV and murine retrovirus infection of T-cells, macrophages and fibroblasts. AST-carboxydextran conjugates will be synthesized, evaluated, and optimized to target the drug to macrophage cells and for retrovirus model systems to evaluate the pharmacokinetics and dynamics of the compounds as well as to determine the ability of polymeric and monomeric carriers to target antivirals to specific tissues. This approach of sustained site-specific delivery of drugs via biodegradable and biocompatible polymers can be extrapolated to improve the therapeutic properties of known anti-AIDS drugs.